Analyses of immunoglobulin (Ig) variable (V) region gene usage in the immune response, estimates ofV gene germline complexity, and other nucleic acid hybridization-based studies depend on the extent to which such genes are related (i. e., sequence similarity) and their organization in gene families. While mouseIgh heavy chainV region (V _H ) gene families are relatively well-established, a corresponding systematic classification ofIgk light chainV region (V _k ) genes has not been reported. The present analysis, in the course of which we reviewed the known extent of theV _k germline gene repertoire andV _k gene usage in a variety of responses to foreign and self antigens, provides a classification of mouseV _k genes in gene families composed of members with >80% overall nucleic acid sequence similarity. This classification differed in several aspects from that ofV _H genes: only someV _k gene families were as clearly separated (by >25% sequence dissimilarity) as typicalV _H gene families; mostV _k gene families were closely related and, in several instances, members from different families were very similar (>80%) over large sequence portions; frequently, classification by nucleic acid sequence similarity diverged from existing classifications based on amino-terminal protein sequence similarity. Our data have implications forV _k gene analyses by nucleic acid hybridization and describe potentially important differences in sequence organization betweenV _H andV _k genes.